1. Field of the Invention
The present invention is related generally to drying systems and, more particularly, to drying systems which are capable of rapidly drying chemical reaction products held in cavities or wells.
2. Description of the Related Art
Combinatorial chemical synthesis permits the production of very large numbers of small molecule chemical compounds which ay, for example, be tested for biological activity. One combinatorial synthesis method employs polymeric resin beads as solid phase substrates upon which small molecule compounds are formed. In this method, sometimes referred to as the "mix and split" method, a sample of beads is divided among several reaction vessels and a different reaction is performed in each vessel. The beads from all the vessels are then pooled and redivided into a second set of vessels, each of which now contains approximately equal amounts of beads carrying the products of the first set of reactions. When a second reaction is performed, each of the products of the first set of reactions acts as a substrate for a new set of reactions which produce all the possible combinations of reactants. The mix and split combinatorial chemical synthesis method is discussed in greater detail in, M. A. Gallop, R. W. Barrett, W. J. Dower, S. P. A. Fodor, and E. M. Gordon, Applications of Combinatorial Technologies to Drug Discovery, 1. Background and Peptide Combinatorial Libraries, Journal of Medical Chemistry 1994, Vol. 37, pp. 1233-1251; E. M Gordon, R. W. Barrett, W. I. Dower, S. P. A. Fodor, M. A. Gallup, Applications of Combinatorial Technologies to Drug Discovery, 2. Combinatorial Organic Synthesis, Library Screening Strategies and Future Directions, Journal of Medical Chemistry 1994, Vol. 37, pp. 1385-1401; M. R. Pavia, T. K. Sawyer, W. H. Moos, The Generation of Molecular Diversity, Bioorg. Med. Chem. Lett. 1993, Vol. 3, pp. 387-396 and M. C. Desai, R. N. Zuckerman, W. H. Moos, Recent Advances in the Generation of Chemical Diversity Libraries, Drug Dev. Res. 1994, Vol. 33 pp. 174-188 which are hereby incorporated by reference. See also, U.S. Pat. No. 5,565,324 which is also hereby incorporated by reference.
By providing an extremely large library of chemical compounds for testing, combinatorial chemical synthesis provides support for the development of compounds which may be used to develop new drugs for treating a wide range of diseases. Rather than painstakingly synthesizing chemicals one at a time and individually testing them for biological activity with, for example, an enzyme involved in heart disease, or a cell receptor involved in fighting cancer, many chemicals can be developed and tested in parallel, greatly accelerating the drug development process and, hopefully, leading to major advances in the treatment and prevention of disease.
Tests, such as those for biological activity, are often performed upon the compounds at a different location from that where they are formed. For convenience of handling and to ease the testing of large numbers of compounds, samples of a variety of compounds are often placed within the wells of a plate which contains an array of wells. Alternatively, each well may contain the same compound, so that a number of tests may be conducted on the same compound simultaneously. Plates such as these are conventional and a number of standard arrays are available, including a ninety-six well plate. Wells within the plates are generally available in either deep or shallow configurations. To reduce spills and the likelihood of cross contamination and to prevent degradation of the samples due, for example, to oxidation, reaction products placed within the wells are dried, by evaporating the solvents and other volatiles in which the chemical products are immersed preferably in an inert atmosphere.
Although the benefits of drying the compounds are several, the time and expense required to dry them using traditional drying systems and techniques can be burdensome. For example, freeze drying the compounds may take several days and many times requires unwanted fillers, such as sugars. Drying by placing the compounds under a controlled vacuum may require between five and ten hours for the drying, assuming shallow well plates. A typical convection based drying oven for drying such compounds may also require on the order of ten hours for a shallow well plate and considerably more for a deep well plate.
One reason for the long drying times is that vapor forms immediately above the samples, and accumulates in the semi-closed volumes of the wells. This vapor slows the drying process. To eliminate the accumulated vapor and thus accelerate drying, some conventional dryers insert jets of inert gas directly into each of the wells. While the dry inert gas does tend to displace the vapor and thus accelerate drying, the introduction of large volumes of inert gas into the vacuum chamber imposes the requirement of a much larger vacuum pump for the system. Additionally, the use of large volumes of inert gas adds considerably to the expense of operating a drying system.
Another technique, the GeneVac.TM. sold by GeneVac Limited of Ipswich, England, employs a centrifuge which holds shallow or deep well plates and spins those plates within an evacuated and heated chamber. While this unit operates relatively quickly, it has the drawbacks of low mechanical reliability, low capacity, difficult loading and unloading, and high expense.
High vacuum ovens may provide the benefit of rapid drying, however, the solvents have been known to be susceptible to spontaneous boiling, also known as "bumping". Bumping can be process critical as it may cause contamination and loss of compound. This is particularly true for low boiling point solvents.
The compounds being evaporated may also include any of a number of corrosive chemicals. A drying system which providers rapid, inexpensive drying of chemical compounds without requiring the use of large volumes of inert gases and which can withstand exposure to corrosive chemicals would therefore be highly desirable. Additionally, it is further desirable to control temperature and pressure in a controlled manner which prevents degradation and bumping without unnecessary moving parts.